Abstract
We determined the contractile responses to newer cardiotonic drugs in isometrically contracting right ventricular papillary muscles isolated from newborn (NB; 24-18 hrs), immature (IM; 14-18 days), and adult (AD; 6-10 months) rabbits. Cumulative dose-response relationships were obtained in each age group to forskolin, an agent that directly stimulates adenylate cyclase activity independent of adrenergic receptors, and to milrinone, a relatively selective inhibitor of high-affinity CAMP phosphodiesterase (PDE) activity. Both drugs increased developed tension and shortened time to peak tension and relaxation time. Tabulated below are results for the maximal rate of tension development (DT/dt) at low and high concentrations of forskolin and milrinone.
The dramatic inotropic response to forskolin in NB myocardium suggests that at birth: 1) myocardial adenylate cyclase activity is well developed, and 2) the PDE system is inadequate to hydrolyze excessive cAMP. The latter conclusion is further supported by the lack of response to milrinone in NB muscles. These findings may have important implications in the design of cardiotonic drugs for use in the immature heart.
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Artman, M., Wicke, J., Kithas, P. et al. MYOCARDIAL CONTRACTILE RESPONSES TO FORSKOLIN AND MILRINONE DURING POSTNATAL MATURATION. Pediatr Res 21 (Suppl 4), 185 (1987). https://doi.org/10.1203/00006450-198704010-00116
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DOI: https://doi.org/10.1203/00006450-198704010-00116